The objective of this research is to investigate the mechanisms which control the proliferation and differentiation of normal and leukemic granulocytes and monocytes. It is proposed to study the structure and function of the regulator granulocyte-macrophage colony stimulating factor (GM-CSF) with subpopulations of bone marrow and leukemic cells. Pure GM-CSF will be radiolabeled with 125I or tritium and its binding to target cells studied. GM-CSF presumably interacts with the membrane of its target cells, and the molecular arrangement of granulocytic and monocytic cells from normal and leukemic populations will be studied. The cell surfaces will be radiolabeled using the lactoperoxidase method or a new flash photolytic method. The membrane proteins will be analyzed by polyacrylamide gel electrophoresis and isoelectric focussing, as well as functionally, in an attempt to detect the GM-CSF receptor and other differentiation or leukemic markers. The molecular changes induced by GM-CSF will be investigated in order to probe its mechanism of action. RNA, DNA and protein synthesis in GM-CSF sensitive cells from bone marrow and a myelomonocytic leukemic tumor will be investigated to determine the initial changes induced by GM-CSF. Subpopulations of granulocytes, monocytes and their progenitor cells will be isolated from normal and leukemic bone marrow blood and peritoneal exudate cells by conventional cell separation techniques sedimentation velocity, density centrifugation, adherence as well as affinity chromatography and fluorescence activated cell sorting. Fluorescent probes will include derivatives of GM-CSF, actin, some chemotactic peptides, specific antigranulocyte sera and lectins.